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The present study investigated prefrontal cortex (PFC) atrophy as a possible predictor of dementia. Eighty-eight older participants of the Maastricht Aging Study (MAAS) were administered for neuropsychological tests at baseline and after three years (t(3)). Magnetic resonance images were acquired at t(3) and nine years after baseline all participants were screened for dementia. Three groups were distinguished: (1) participants who did not develop dementia or cognitive decline, (2) participants who did not develop dementia but did show significant cognitive decline, and (3) participants who developed dementia. Gray matter volume of structures in the PFC and medial temporal lobe (MTL) was measured. Prefrontal volume was significantly smaller in group 3 than in the other two groups, and PFC volume was significantly better than MTL volume in distinguishing between groups 2 and 3. These findings suggest that PFC atrophy is highly associated with dementia and can be considered an important predictor of the disease. It may even be a better predictor than the MTL atrophy that has been found in earlier studies.